Antibodies to nucleic acids are important diagnostically and pathogenetically in systemic lupus. The production of these antibodies is in part controlled by the X-chromosome through regulation of maturation of B cells destined to make IgM antibodies to nucleic acids. Sex chromosomes indirectly influence the magnitude to auto-antibody production through sex hormones: male sex hormones suppress the production of anti-nucleic acid antibodies. Hybridoma cells producing anti-nucleic antibodies (derived originally by fusing BALB/c and NZB x NZW F1 cells) preferentially grow and preferentially produce different autoantibodies in different recipient strains. These studies suggest that control mechanisms exist for the proliferation of, and perhaps synthesis by, B cells genetically destined to produce antibodies to nucleic acids. Antibodies specific for anti-RNA or anti-DNA antibodies can be produced and used to study the regulation of autoantibody production.